Rift valley Fever virus (RVFv) causes devastating livestock epizoonotics and concurrent human epidemics in sub-Saharan Africa and the Middle East. Observations of humans with RVF and primates experimentally challenged with RVFv suggest that the initial, rapid upregulation of type I IFN impacts the level and duration of viremia, limits the severity of morbidity, retinitis and encephalitis. Recover from primary infection is also dependent on the development of neutralizing IgG antibodies. This project addresses gaps in knowledge about RVFv infection by integrating clinical studies of Kenyan participants with laboratory investigations of cellular immunity and genetic susceptibility. We hypothesize that heterogeneities in the clinical phenotype of human RVF are determined by the intensity and route of RVFV transmission, and innate and adaptive immune responses determined by host genetics.